Nephrotic Syndrome – Interesting Facts, Symptoms, Diagnosis and Treatment

What is Nephrotic Syndrome

Nephrotic syndrome occurs when the kidneys’ filters (glomeruli) are damaged.

Glomeruli remove toxins and waste products from the bloodstream. As a result of damaged glomeruli, essential products such as proteins may also be removed from the bloodstream.

Nephrotic syndrome is a set of findings that show there is a problem with the kidneys.

These findings include:

• High levels of protein in the urine (proteinuria).
• High blood pressure (hypertension).
• Low levels of the protein albumin in the blood (hypoalbuminemia).
• High levels of cholesterol (hyperlipidemia) and triglycerides (hypertriglyceridemia) in the blood.
• Swelling (edema) of the face, abdomen, arms, and legs.

Nephrotic syndrome is one of the most rigidly defined entities in clinical medicine. The term is not a specific diagnosis, but instead represents a cluster of abnormal findings.

5 Interesting Facts of Nephrotic syndrome

1. The nephrotic syndrome is comprised of four distinct elements

a. edema

b. massive proteinuria, defined as a urine protein:creatinine ratio >2 (mg:mg) in children and >3.5 g/24 hours in adults

c. hypoalbuminemia

d. hypercholesterolemia

e. with an optional fifth feature, a hypercoagulable state

2. Nephrotic syndrome is classified as primary (or idiopathic) and secondary causes. There are four principal primary etiologies:

a. Minimal change nephrotic syndrome (MCNS)

b. Focal segmental glomerulosclerosis (FSGS)

c. Membranous nephropathy (MN)

d. Membranoproliferative glomerulonephritis (MPGN)

3. A kidney biopsy is necessary to definitively distinguish among the four causes of primary nephrotic syndrome or confirm a secondary cause. Genetic testing may be an alternative diagnostic test in infants in the first year of life or in those with a family history of disease.

4. The natural history of primary nephrotic syndrome depends on the underlying cause. Patients with MCNS have an excellent long-term prognosis. Half of patients with primary FSGS will progress to end-stage kidney disease over 5 to 10 years. Additionally, 25% to 30% of primary FSGS patients develop recurrent disease following a kidney transplant.

5. Corticosteroids are generally considered the first agent to be tried to reduce proteinuria in all patients with nephrotic syndrome, unless there is a clinical contraindication to their use. Calcineurin inhibitors are the most widely accepted second-line therapeutic option in patients with nephrotic syndrome who are unresponsive to corticosteroids or who are experiencing significant side effects.

Specifically, it is comprised of four distinct elements: one physical sign, edema; and three laboratory test abnormalities, massive proteinuria, hypoalbuminemia, and hypercholesterolemia.

A hypercoagulable state is an optional fifth feature, especially in adults, who have a 10-fold higher risk of thromboembolic complications compared to pediatric patients.

The hypercoagulable state in the nephrotic syndrome is due to many factors including urinary loss of antithrombin III, increased platelet aggregation, and endothelial dysfunction.

It is important to note that reduced glomerular filtration rate or azotemia is not a defining feature of the nephrotic syndrome in any age group.

Edema is a key feature in patients with nephrotic syndrome. Studies suggest that it can develop by two distinct mechanisms.

According to the underfill hypothesis, the hypoalbuminemia leads to decreased plasma oncotic pressure, reduction in the effective intravascular compartment size, activation of the renin–angiotensin axis, and stimulation of renal sodium reabsorption.

In contrast, the overfill hypothesis posits that sodium retention in nephrotic syndrome is a primary abnormality in the kidney due to corin-mediated activation of the epithelial sodium channel.

It is likely most patients have a component of each mechanism operating in the formation of edema. In most cases, the edema is controlled with modest dietary salt restriction and the administration of diuretics.

In cases with severe underfilling, infusions of albumin and furosemide may be required to control edema.

Nephrotic syndrome results from the loss of proteins and other substances that the body needs. Nephrotic syndrome may increase your risk of further kidney damage and of health problems such as blood clots and infections.

What are the causes?

Nephrotic Syndrome may be caused by:

• A kidney disease that damages the glomeruli, such as:
  • Minimal change disease.
  • Focal segmental glomerulosclerosis.
  • Membranous nephropathy.
  • Glomerulonephritis.
• A condition or disease that affects other parts of the body (systemic), such as:
  • Diabetes.
  • Autoimmune diseases, such as lupus.
  • Amyloidosis.
  • Multiple myeloma.
  • Some types of cancers.
  • An infection, such as hepatitis C.
• Certain medicines, such as:
  • Nonsteroidal anti-inflammatory drugs (NSAIDs).
  • Some anticancer drugs.

In some cases, the cause may not be known.

What are the symptoms of Nephrotic Syndrome?

Symptoms of Nephrotic Syndrome include:

• Edema.
• Foamy urine.
• Unexplained weight gain.
• Loss of appetite.

In some cases, there are no noticeable symptoms.

How is Nephrotic Syndrome diagnosed?

Nephrotic Syndrome is usually diagnosed with a dipstick urine test followed by a 24-hour urine test in which you collect all of the urine that you produce over a 24-hour period. If your test shows that you have this condition, more tests may be needed to find the cause.

These may include blood, urine, imaging, or kidney biopsy tests.

How is Nephrotic Syndrome treated?

Treatment for Nephrotic Syndrome may include medicines to control symptoms or to prevent complications from occurring. These medicines may:

• Decrease inflammation in the kidneys.
• Lower blood pressure.
• Lower cholesterol.
• Reduce the blood’s ability to clot.
• Help control edema.

Further treatment will depend on the cause of the Nephrotic Syndrome. Your health care provider will discuss treatment options with you.

Follow these instructions at home:

• Follow diet instructions from your health care provider. This may include changes to help manage edema or hypertension, such as limiting your intake of salt or fluids.
• Take over-the-counter and prescription medicines only as told by your health care provider.
  • Do not take any new over-the-counter medicines or nutritional supplements unless approved by your health care provider. Many medicines can make this condition worse. Doses may need to be adjusted.
• Keep all follow-up visits as told by your health care provider. This is important.

Contact a health care provider if:

• Your symptoms do not go away as expected or you develop new symptoms.
• You continue to gain weight.
• You have increased swelling of the feet, ankles, or legs.

Get help right away if:

• You stop producing urine.
• You have prolonged bleeding.
• You have shortness of breath.
• You have a severe headache.
• You have severe weakness.